Autonomic neuropathy is a major and relatively frequent complication of human diabetes mellitus. Little is known about the pathology and pathogenesis of the neuropathy. An experimental neuropathologic model of the disorder has not been developed. The objective of the proposed research is the development of an experimental neuropathologic model of diabetic autonomic neuropathy. The Principal Investigator has demonstrated pathologic evidence of an autonomic neuropathy in rats with streptozotocin-induced diabetes. In the course of the proposed investigation the pathologic characteristics of the neuropathy will be identified more completely by morphometric, ultrastructural, and histochemical methods. The relationship of the neuropathy to sorbitol metabolism will be explored. The effects of pancreatic islet transplant and nutritional factors on the progress of the neuropathy will be evaluated. The occurrence and frequency of autonomic lesions in human diabetes similar to those in diabetic rats will be determined. Information necessary to develop and establish a convenient, reliable experimental neuropathologic model of diabetic autonomic neuropathy will be obtained. The availability of such a model would facilitate the study of methods for controlling or preventing human diabetic autonomic neuropathy.